The overall objective of this project is to study the dietary and hormonal regulation of fatty acid metabolism. Diabetes mellitus decreases fatty acid synthesis by decreasing the synthesis of fatty acid synthetase. Insulin injection to diabetic animals induces fatty acid synthetase. We plan to study the role of insulin and related hormones on the synthesis of fatty acid synthetase in intact animals and in cultured cells. Attempts are being made to isolate and characterize the mRNA of the synthetase. The large size of the synthetase mRNA is being considered in developing procedures for its isolation. Translation of the mRNA in a cell free system has been achieved. The effect of insulin on the formation and stability of the mRNA and its translation by the ribosomes will be studied. The effect of insulin, cortisol and prolactin on the induction of fatty acid synthetase and the lipogenic enzymes in mammary gland explants will be investigated. Methodology to be employed in the outlined studies include enzymology, protein chemistry, lipid chemistry and cell biology.